The CRF1 receptor mediates social behavior deficits induced by opiate withdrawal.
J Neurosci Res. 2020-07-29; :
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Poor sociability and aggressive behavior are key clinical features of opioid use
disorders. The corticotropin-releasing factor (CRF) system may mediate behavioral
effects of substances of abuse but its implication in substance-induced social
behavior deficits and outward-directed hostility remains largely unknown. CRF
signaling is mediated by two receptor types, termed CRF1 and CRF2 . The present
study aimed at understanding the role for the CRF1 receptor in social and
aggressive behavior induced by withdrawal from repeated opiate administration.
Thus, wild-type (CRF1 +/+), CRF1 receptor heterozygous (CRF1 +/-), and null
mutant (CRF1 -/-) female and male mice were treated with saline or escalating
doses of morphine (20-100 mg/kg, i.p.) during six consecutive days and tested in
the three-chamber task for sociability (i.e., preference for an unfamiliar
same-sex conspecific vs. an object) 7 days after the last administration.
Moreover, aggressive biting behavior toward the unfamiliar conspecific was
assessed during the three-chamber test. Opiate withdrawal disrupted sociability
in CRF1 +/+ and CRF1 +/-, but not in CRF1 -/-, female mice, without affecting
aggressive biting behavior in any genotype. In contrast, opiate withdrawal did
not affect sociability but increased aggressive biting behavior in male mice,
independently of CRF1 receptor-deficiency. Nevertheless, in opiate-withdrawn CRF1
+/+, but not CRF1 +/- and CRF1 -/-, male mice, sociability directly correlated
with aggressive biting behavior, suggesting a role for the CRF1 receptor in
hostility-linked social approach. These findings demonstrate the implication of
the CRF1 receptor in social behavior deficits associated with repeated opiate
administration and withdrawal, revealing a new potential target for the treatment
of opioid use disorders.